Quinoprotein methanol dehydrogenase: a molecular dynamics study and comparison with crystal structure |
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Authors: | Swarnalatha Y. Reddy Thomas C. Bruice |
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Affiliation: | a Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA b Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA c DuPont Agricultural Products, Stine-Haskell Research Center, Newark, DE 19714, USA |
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Abstract: | One of the mechanisms proposed for methanol oxidation by methanol dehydrogenase (MDH) involves a hydride transfer to the quinone carbonyl carbon C5 of 2,7,9-tricarboxy-1H-pyrrolo[2,3-f]-quinoline-4,5-dione (PQQ), initiated by abstraction of a proton from the substrate methanol by a general base. Molecular dynamics studies are performed on MDH-bound to the C5 reduced intermediate (C5RI) of PQQ, for 3 ns. The structural features of the MD and X-ray structures are compared. An interesting feature observed during simulations is the strong hydrogen bond between oxyanion O5 of C5RI and Asp297-CO2H in the active site. Asp297-CO2− is suggested to be the general-base catalyst for removing the hydroxyl proton of methanol in concert with the hydride ion transfer from the putative methoxide to C5 carbonyl of PQQ. The formed Asp297-CO2H acts as the required proton source for the immediate product. Anticorreleated motions observed in the MD structure are not across the active site to influence the reaction mechanism of MDH. |
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Keywords: | Quinoprotein Methanol dehydrogenase 2,7,9-Tricarboxy-1H-pyrrolo[2,3-f]-quinoline-4,5-dione Molecular dynamics |
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